The general objective of this proposal is to gain a comprehensive understanding of inherited disorders of cellular transport resulting in renal aminoacidurias and melliturias and of inherited abnormalities of human galactose metabolism. The underlying approach continues to be the application of biochemical techniques to delineate basic alterations of cellular function resulting from deranged genetic expression. Various model systems will be employed ranging from the intact animal to cellular and subcellular fractions. Aspects of renal tubule cell transport to be examined are: 1) brush border membrane structure and function, 2) developmental characteristics of amino acid and sugar transport focusing on regulation and control mechanisms, 3) the role of the gamma glutamyl cycle in amino acid transport, and 4) the mechanism of cystinuria in stone-forming dogs as a model for human cystinuria. Features of galactose metabolism to be studied are: 1) the biochemical etiology of galactose toxicity in brain that may be responsible for mental retardation, 2) galactose utilization and its control in the perfused rat liver of the young and adult animal and the nature of galactose-induced derangements of hepatic function, 3) the use of tissue culture cells from galactosemic patients to discern the metabolic consequences of abnormal galactose metabolism.